Many studies demonstrate that stress exposure in childhood is associated with multiple kinds of illnesses in adulthood. The mechanisms underlying these associations are not yet clear, but there is consideration speculation that inflammation and, more broadly, alteration of the immune system from early stress exposure has an etiological role. What has not been established is the extent to which, and the mechanisms by which, early stress exposure has childhood onset effects on the immune system. Research is now needed to translate adult and a sizable experimental animal literature to pediatric samples; results from these studies would fundamentally shape public and clinical health approaches. The proposed study makes use of the Family Life Project (FLP), an ongoing prospective longitudinal study of 1292 children who were selected using epidemiological methods to oversample stress-exposed children. Indicators of innate and adaptive immune function will be collected from detailed developmental visits when the children are approximately 9 years of age and linked with measures of stress, behavior and psychosocial context data dating back to 2 months of age. Several features of the proposed study provide particular leverage for advancing this field of research, including a) a large epidemiologically-derived sample of pre-adolescent children at elevated psychosocial risk who have been carefully studied since infancy, b) detailed study of the innate and adaptive immune systems, and c) detailed assessment of socio-demographic and proximal family stress across the first decade of life that provide leverage for testing hypotheses about the type and timing of stress exposure, and d) examination of glucocorticoid resistance as a mediating mechanism. The research aims are to 1) test alternative hypotheses for a link between stress exposures and components of the innate immune system; 2) examine the association between early stress exposure and adaptive immunity, indexed by T cell responses to latent/persistent virus; and 3) determine the associations between behavioral/emotional and somatic symptoms and immune function in stress-exposed children. We also add a fourth exploratory aim: to examine the links between family and socio-demographic risk and illness and functional outcomes. The proposed study will add significant new information to our understanding of if and how stress exposure is associated with childhood onset dysregulated immune outcomes and the mechanisms involved. Findings from the study will provide a much-needed empirical foundation for developmental and clinical models of the interplay between stress and health in children.